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Title: Investigating remission and relapse in type 1 diabetes. Immune correlates of clinical outcome in beta-cell replacement therapies

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Cover Page

The handle http://hdl.handle.net/1887/47907 holds various files of this Leiden University dissertation.

Author: Torren, C.R. van der

Title: Investigating remission and relapse in type 1 diabetes. Immune correlates of clinical outcome in beta-cell replacement therapies

Issue Date: 2017-04-12

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Investigating Remission and Relapse in Type 1 Diabetes

Immune Correlates of Clinical Outcome in

Beta-Cell Replacement Therapies

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Investigating Remission and Relapse in Type 1 Diabetes

Immune Correlates of Clinical Outcome in Beta-Cell Replacement Therapies

Proefschrift

ter verkrijging van de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties te verdedigen op woensdag 12 april 2017

klokke 13:45 uur

door

Cornelis Rudolf van der Torren geboren te Heerlen in 1984 Cover design and lay-out: C.R. van der Torren

Cover image: designer MedicalGraphics.de (license: CC BY-ND 3.0 DE) Printed by: Gildeprint

ISBN: 978-94-6233-584-4

©2017 C. R. van der Torren.

All rights reserved. No part of this publication may be reproduced in any form or by any means without prior permission of copyright owner.

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Contents

Chapter 1. General Introduction

Chapter 2. Immune intervention trials towards a cure for type 1 diabetes De (om)Weg naar Genezing van Type 1 Diabetes 17 Chapter 3. Fate of Transplanted Islets, Local Insights

Identification of Donor Origin and Condition of Transplanted

Islets in situ in the Liver of a Type 1 Diabetic Recipient 29 Chapter 4. Immune Biomarkers of Islet Transplantation Outcome

A Pre-Transplant GAD-Autoantibody Status to Guide Prophylactic Antibody Induction Therapy in Simultaneous

Pancreas and Kidney Transplantation. 45

B Serum Cytokines as Biomarkers in Islet Cell Transplantation

for Type 1 Diabetes 59

Chapter 5. Consequences of Reducing Immunosuppressive Burden in Islet Transplantation

A Immune Responses against Islet Allografts during Tapering of

Immunosuppression - a Pilot Study in 5 Subjects 75 B Predictive Factors of Allosensitization following

Immunosuppressant withdrawal in Recipients of Long-Term

Cultured Islet Cell Grafts 89

Chapter 6. Immunogenicity of Beta-Cells from Alternative Sources A Innate and Adaptive Immunity to Human Beta-Cell Lines:

Implications for Beta-Cell Therapy 105

B Immunogenicity of Human Embryonic Stem Cell-derived

Beta-Cells 115

Chapter 7. General Discussion

R References & Abbreviations 141

& Summary 161

& Samenvatting 165

& Acknowledgements 169

& Curriculum Vitae 170

& Publications 171

PROMOTOREN

Prof.dr. B.O. Roep

Prof.dr. P. Gillard (Katholieke Universiteit Leuven, Belgium)

PROMOTIECOMMISSIE

Prof.dr. E.J.P. de Koning Dr. W. Oostdijk

Dr. A.A. van Apeldoorn (Maastricht University)

Prof.dr. K. Buschard (The Bartholin Institute, Copenhagen, Denmark)

The work presented in this thesis was supported by the European Commission (FP6 and BetaCellTherapy, number 241883 in the FP7 program), Dutch Diabetes Research Foundation, the Juvenile Diabetes Research Foundation.

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